Isoquinoline derivatives are a group of nitrogen-containing organic compounds existing in plants and animals in nature. Most of them have a complex ring structure with their nitrogen atom incorporated in the ring. Such isoquinoline derivatives, including salsolinol and reticuline, possess significant biological activities. Salsolinol is known to be used mainly for regulation of blood pressure, while reticuline is used mainly as an active ingredient for treating malaria, and also as a component in pain relievers.
It is disclosed in U.S. patent application Ser. No. 14/492,547 that isoquinoline derivatives, including salsolinol and reticuline, can activate AMP-dependent protein kinase (AMPK) and use in treatment of AMPK-dependent diseases. However, no prior art references report the effect of isoquinoline derivatives in treatment of diabetic wound healing.
Diabetes mellitus can be virtually harmless if controlled, but the state of abnormally high blood glucose levels associated with the condition can lead to some serious complications. If left uncontrolled for a long time, or if diabetic patients fail to adapt their lifestyles in order to manage the disease, they will have more difficulty preventing complications from occurring. A serious complication that diabetics may encounter is diabetic wounds.
The main concern with diabetic wounds is poor or delayed healing. Healing problems are caused by the peripheral arterial diseases and peripheral neuropathy that can occur with diabetes, wherein the small blood vessels in different parts of the body, especially in the extremities (hands and feet), grow narrower and reduce the blood circulation to those areas. A lack of circulation in the extremities can result in a reduced supply of oxygen and nutrients to the body tissue and nerves, which is necessary for healing. Over time, nerves in these areas may become damaged, decreasing the sensation of pain, temperature and touch, making patients vulnerable to injury.
There is a long felt need in the art for methods to treat diabetic wounds. The present invention satisfies this need.